Heat-shock protein induction in rat hearts: A direct correlation between the amount of heat-shock protein induced and the degree of myocardial protection

Background: Previous studies have demonstrated that heat-shock treatment results in the induction of 72-kD heat-shock protein (HSP72) and a reduction of infarct size after subsequent ischemia and reperfusion. Methods and Results: To test the hypothesis that the degree of protection from ischemic injury in heat-shocked rats correlates with the degree of prior HSP72 induction, rats pretreated with 40°C, 41°C, or 42°C of whole-body hyperthermia followed by 24 hours of recovery and control rats (n=6 in each group) were quantitatively assessed for the presence of myocardial HSP72 by optical densitometry of Western blots and a primary antibody that is specific for HSP72 and a tertiary antibody labeled with ¹²⁵I. Although rats heat- shocked to 40°C had no significant induction of myocardial HSP72, rats heat- shocked to 41°C and 42°C demonstrated progressively increased amounts of myocardial HSP72 compared with controls. Separate groups of rats heat- shocked to 40°C (n=16), 41°C (n=37), and 42°C (n=36) with 24 hours of recovery and controls (n=26) were subjected to 35 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Compared with control and 40°C rats, there was progressive infarct size reduction, assessed by triphenyltetrazolium chloride staining, in rats that were heat-shocked to 41°C and 42°C. Furthermore, there was a direct correlation between the amount of HSP72 induced and the reduction in infarct size (r=.97, P=.037). Conclusions: These results suggest that the improved salvage after heat- shock pretreatment may be related to the amount of HSP72 induced before prolonged ischemia and reperfusion.